p63 promotes cell survival through fatty acid synthase

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p63 promotes cell survival through fatty acid synthase

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dc.contributor.author Di Napoli, Arianna
dc.contributor.author Seeley, Apryle
dc.contributor.author Amato, Angela M.
dc.contributor.author O'Regan, Esther
dc.contributor.author Sabbisetti, Venkata S
dc.contributor.author Ghebremichael, Musie Syum
dc.contributor.author Loda, Massimo
dc.contributor.author Signoretti, Sabina
dc.date.accessioned 2011-04-29T04:26:36Z
dc.date.issued 2009
dc.identifier.citation Sabbisetti, Venkata, Arianna Di Napoli, Apryle Seeley, Angela M. Amato, Esther O'Regan, Musie Ghebremichael, Massimo Loda, and Sabina Signoretti. 2009. p63 promotes cell survival through fatty acid synthase. PLoS ONE 4(6): e5877. en_US
dc.identifier.issn 1932-6203 en_US
dc.identifier.uri http://nrs.harvard.edu/urn-3:HUL.InstRepos:4879208
dc.description.abstract There is increasing evidence that p63, and specifically ΔNp63, plays a central role in both development and tumorigenesis by promoting epithelial cell survival. However, few studies have addressed the molecular mechanisms through which such important function is exerted. Fatty acid synthase (FASN), a key enzyme that synthesizes long-chain fatty acids and is involved in both embryogenesis and cancer, has been recently proposed as a direct target of p53 family members, including p63 and p73. Here we show that knockdown of either total or ΔN-specific p63 isoforms in squamous cell carcinoma (SCC9) or immortalized prostate epithelial (iPrEC) cells caused a decrease in cell viability by inducing apoptosis without affecting the cell cycle. p63 silencing significantly reduced both the expression and the activity of FASN. Importantly, stable overexpression of either FASN or myristoylated AKT (myr-AKT) was able to partially rescue cells from cell death induced by p63 silencing. FASN induced AKT phosphorylation and a significant reduction in cell viability was observed when FASN-overexpressing SCC9 cells were treated with an AKT inhibitor after p63 knockdown, indicating that AKT plays a major role in FASN-mediated survival. Activated AKT did not cause any alteration in the FASN protein levels but induced its activity, suggesting that the rescue from apoptosis documented in the p63-silenced cells expressing myr-AKT cells may be partially mediated by FASN. Finally, we demonstrated that p63 and FASN expression are positively associated in clinical squamous cell carcinoma samples as well as in the developing prostate. Taken together, our findings demonstrate that FASN is a functionally relevant target of p63 and is required for mediating its pro-survival effects. en_US
dc.language.iso en_US en_US
dc.publisher Public Library of Science en_US
dc.relation.isversionof doi:10.1371/journal.pone.0005877 en_US
dc.relation.hasversion http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2691576/pdf/ en_US
dash.license LAA
dc.subject cell biology en_US
dc.subject developmental biology en_US
dc.subject urology en_US
dc.subject oncology en_US
dc.subject head and neck cancers en_US
dc.subject pathology en_US
dc.subject molecular pathology en_US
dc.title p63 promotes cell survival through fatty acid synthase en_US
dc.type Journal Article en_US
dc.description.version Version of Record en_US
dc.relation.journal PLoS ONE en_US
dash.depositing.author Sabbisetti, Venkata S
dc.date.available 2011-04-29T04:26:36Z
dash.affiliation.other HMS^Medicine-Brigham and Women's Hospital en_US
dash.affiliation.other SPH^Biostatistics en_US
dash.affiliation.other HMS^Pathology en_US
dash.affiliation.other HMS^Pathology en_US

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